title: An ATP-sensitive potassium (KATP) channel opener, nicorandil, lowers the threshold for ischemic preconditioning in barbital-anesthetized dogs.
abstract: To determine whether the adenosine triphosphate (ATP)-sensitive potassium channel (KATP channel) opener, nicorandil, lowers the threshold for the infarct-reducing effect of preconditioning (PC), barbital-anesthetized dogs were subjected to 60-min occlusion (60'OC) of left anterior descending coronary artery (LAD) followed by 3-h reperfusion (3h-RP). At the end of the 3h-RP, heart was resected to measure infarct size. Infarct size was determined by triphenyltetrazolium chloride (TTC) staining, calculated gravimetrically and was expressed as a percent age of area at risk (AAR). Myocardial blood flow was measured by radioactive microspheres. Single 5-min LAD occlusion 10 min before 60'OC (5'PC group) markedly reduced infarct size, compared to the controls (11.8 +/- 3.7% versus 26.8 +/- 4.7%; P < 0.05). Neither 2.5-min PC (2.5'PC group), nor 2.5-min intracoronary infusion with 0.5 microgram/kg per min of nicorandil followed by a 10-min drug-free period (2.5'NC group), showed a cardioprotective effect (26.5 +/- 1.7% and 20.7 +/- 2.8%, respectively). However, when nicorandil was administered during the 2.5-min LAD occlusion period (2.5'PC + 2.5'NC group), infarct size was significantly reduced to an extent similar to that in 5'PC group (13.6 +/- 1.2%). There were no significant differences in hemodynamics, collateral circulation, or AAR between groups. These results suggest that nicorandil lowers the threshold for the infarct-reducing effect of PC in dogs by, at least in part, activation of myocardial KATP channels.
authors.affiliation: Second Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mizumura
authors.forename: S
authors.initials: S
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Ozawa
authors.forename: K
authors.initials: K
authors.lastname: Kanmatsuse
authors.forename: G J
authors.initials: GJ
authors.lastname: Gross
mesh_terms: D000818:Animals; D001462:Barbital; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D015221:Potassium Channels / Q000819:agonists*; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors
chemical_list: D015221:Potassium Channels; D009536:Niacinamide; D020108:Nicorandil; D001462:Barbital